Abstract

Inflammatory response has been reported to contribute to the renal lesions in rat Thy-1 nephritis (Thy-1N) as an animal model of human mesangioproliferative glomerulonephritis (MsPGN). Besides C5b-9 complex, C5a is also a potent pro-inflammatory mediator and correlated to severity of various nephritic diseases. However, the role of C5a in mediating pro-inflammatory cytokine production in rats with Thy-1N is poorly defined. In the present studies, the levels of C5a, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were first determined in the renal tissues of rats with Thy-1N. Then, the expression of IL-6 and TNF-α was detected in rat glomerular mesangial cells (GMC) stimulated with our recombinant rat C5a in vitro. Subsequently, the activation of mitogen-activated protein kinase (MAPK) signaling pathways (p38 MAPK, ERK1/2 and JNK) and their roles in the regulation of IL-6 and TNF-α production were examined in the GMC induced by C5a. The results showed that the levels of C5a, IL-6 and TNF-α were markedly increased in the renal tissues of Thy-1N rats. Rat C5a stimulation in vitro could up-regulate the expression of IL-6 and TNF-α in rat GMC, and the activation of MAPK signaling pathways was involved in the induction of IL-6 and TNF-α. Mechanically, p38 MAPK activation promoted IL-6 production, while either ERK1/2 or JNK activation promoted TNF-α production in the GMC with exposure to C5a. Taken together, these data implicate that C5a induces the synthesis of IL-6 and TNF-α in rat GMC through the activation of MAPK signaling pathways.

Highlights

  • Human mesangioproliferative glomerulonephritis (MsPGN) is a renal disease characterized by glomerular mesangial cell (GMC) apoptosis and proliferation as well as extracellular matrix (ECM) secretion [1,2,3,4]

  • The expression of proinflammatory cytokines including IL-6 and tumor necrosis factor-α (TNF-α) is obviously up-regulated in the renal tissues and related to the pathological changes of rat Thy-1 nephritis (Thy-1N) [18, 24]

  • Our current studies found that the production of C5a, IL-6 and TNF-α was markedly increased in the renal tissues of rats with Thy-1N

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Summary

Introduction

Human mesangioproliferative glomerulonephritis (MsPGN) is a renal disease characterized by glomerular mesangial cell (GMC) apoptosis and proliferation as well as extracellular matrix (ECM) secretion [1,2,3,4]. Inflammatory response has been considered to be an important contributor to the development of MsPGN [5,6,7]. Rat Thy-1 nephritis (Thy-1N) is a PLOS ONE | DOI:10.1371/journal.pone.0161867. C5a Induces the Synthesis of IL-6 and TNF-α in GMC Rat Thy-1 nephritis (Thy-1N) is a PLOS ONE | DOI:10.1371/journal.pone.0161867 September 1, 2016

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